Ontogeny of Estrogen Receptor (ER) α and β in the Female Reproductive Tissues of Mice Neonatally Exposed to Diethylstilbestrol

Abstract

Ontogenical expression of estrogen receptor (ER) isoforms, ERα and ERβ, was examined in order to study the roles of the isoforms in the morphogenesis of neonatal diethylstilbestrol (DES) treatment in the female reproductive tissues using an immunohistochemical method. The intensity of ERα immunostaining gradually increased with aging in the epithelial cells of oviducts, uteri, cervices and vaginae in the vehicle-treated control animals. Neonatal DES-treatment up-regulated the expression of ERα in the epithelial cells in these tissues and down-regulated it in the stromal cells at least until 10 days of age including the period of DES-treatment. On day 21, both control and DES-mice showed almost similar ERα distribution in these tissues. There were no differences in the ERα distribution in the ovaries of two experimental groups. ERα was localized in the theca cells and some stromal cells located interfollicularly. Neonatal DES exposure did not influence the distribution pattern of ERβ protein during the period of treatment and postnatal development. The nuclear ERβ-immunoreaction was seen in the granulosa cells of ovaries but not in the cells of reproductive tracts. These results demonstrated that ERα is the critical ER isoform for the estrogen-dependent responses in the normal female genital tract, and that the presence of ERα in the epithelial cells during the period of DES exposure should play important roles in the the induction of abnormal characteristics in the genital tract of DES-mice.